Heparin-free Cardiopulmonary Bypass and Early Systemic Inflammatory Response_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YAN Yang , YAN Luqin , GENG Xigang .

Department of Cardiovascular Surgery，the First Affiliated Hospital，Xi’an Jiaotong University，Xi’an 710061，P. R. China;

Corresponding author：

Keywords：

Heparin-free; 　Cardiopulmonary bypass; 　Protamine - agarose gel; 　Inflammatory factor

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Abstract：　Objective　To explore the feasibility of using protamine-agarose gel to achieve heparin-free cardiopulmonary bypass （CPB）.　Methods　A total of 12 healthy adult dogs were chosen, the dogs were between 2-3 years old,either male or female, with their mean body weight of 23.3±3.7 kg （ranging from 20 to 28 kg）. All the dogs were randomly divided into two groups with 6 dogs in each group. In the heparinized group, conventional CPB technique was used; in the non-heparinized group, protamine-agarose gel column was used to absorb plasma clotting factors in CPB without use of heparin. At the beginning of CPB and 1 h, 2 h, 3 h after CPB, arterial blood samples were collected from dogs in both groups. The expression levels of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and interleukin-8 （IL-8） were measured by enzyme-linked immunosorbent assay（ELISA）and compared.　Results　There was no thrombus formation in the membrane oxygenators during CPB by naked eye observation in both groups. Activated coagulation time （ACT） was always greater than 480 s during CPB. The vital signs of the dogs were all stable during CPB. At the beginning of CPB, there was no statistical difference in plasma concentrations of TNF-α, IL-6, IL-8 between the two groups. At 1 h, 2 h and　3 h after CPB, the expression levels of TNF-α and IL-8 of the non-heparinized group were significantly higher than those of the heparinized group （CPB 3 h TNF-α：156.48±16.65 ng/L vs. 115.87±15.63 ng/L, t=4.356, P=0.001；CPB 3 h IL-8：365.38±46.18 ng/L vs. 299.29±34.50 ng/L, t=2.808, P=0.019）. There was no statistical difference in the expression level of IL-6 between the two groups （P＞0.05）.　Conclusion　Using protamine-agarose gel to absorb plasma clotting factors is an effective technique to establish heparin-free CPB. But this method can induce significant systemic inflammatory response.

Citation： YAN Yang,YAN Luqin,GENG Xigang .. Heparin-free Cardiopulmonary Bypass and Early Systemic Inflammatory Response. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2012, 19(4): 414-418. doi: Copy

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13.	Welters ID， Feurer MK， Preiss V， et al. Continuous S- （＋）-ketamine administration during elective coronary artery bypass graft surgery attenuates pro-inflammatory cytokine response during and after cardiopulmonary bypass. Br J Anaesth， 2011， 106 （2）：172-179.
14.	Morgan C， Zappitelli M， Gill P. Statin prophylaxis and inflammatory mediators following cardiopulmonary bypass：a systematic review. Crit Care， 2009， 13 （5）：R165.
15.	Martínez-Comendador JM， Alvarez JR， Mosquera I， et al. Preoperative statin treatment reduces systemic inflammatory response and myocardial damage in cardiac surgery. Eur J Cardiothorac Surg， 2009， 36 （6）：998-1005.
16.	余杨，何德沛，申林，等. 核转录因子-κB抑制剂对体外循环肺损伤的保护作用. 中国胸心血管外科临床杂志， 2007， 14 （5）：86-88.

1. 　Cohen M.Heparin-induced thrombocytopenia and the clinical use of low molecular weight heparins in acute coronary syndromes. Semin Hematol， 1999， 36 （1 Suppl 1）：33-36.
2. 　Greinacher A. Treatment of heparin-induced thrombocytopenia. Thromb Haemost， 1999， 82 （2）：457-467.
3. 　Levy JH， Adkinson NF Jr. Anaphylaxis during cardiac surgery：implications for clinicians. Anesth Analg， 2008， 106 （2）：392-403.
4. 　Parker JT， Beutler DS， Sukavaneshvar S， et al. Mitigation of coagulation by removing clotting factors part 1：In vitro feasibility study. ASAIO J， 2007， 53 （4）：415-420.
5. 　Sukavaneshvar S， Parker JT， Beutler DS， et al. Mitigation of coagulation by removing clotting factors part 2：Heparin-free extracorporeal circulation in a porcine model. ASAIO J， 2007， 53 （4）：421-427.
6. 　Wan S， Leclerc JL， Vincent JL. Cytokine responses to cardiopulmonary bypass：lessons learned from cardiac transplantation. Ann Thorac Surg， 1997， 63 （1）：269-276.
7. 　Taylor KM. SIRS--the systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg， 1996， 61 （6）：1607-1608.
8. 　Tilg H， Dinarello CA， Mier JW. IL-6 and APPs：anti-inflammatory and immunosuppressive mediators. Immunol Today， 1997， 18 （9）：428-432.
9. 　Franke A， Lante W， Fackeldey V， et al. Pro-inflammatory cytokines after different kinds of cardio-thoracic surgical procedures：is what we see what we know? Eur J Cardiothorac Surg， 2005， 28 （4）：569-575.
10. 　Huang H， Yao T， Wang W， et al. Combination of balanced ultrafiltration with modified ultrafiltration attenuates pulmonary injury in patients undergoing open heart surgery. Chin Med J （Engl）， 2003， 116 （10）：1504-1507.
11. 　王电军，尹邦良，喻风雷，等．间断肺通气对体外循环肺损伤的保护作用．中国胸心血管外科临床杂志， 2005， 12 （2）：86-88．.
12. 　Guo HW， Wang WJ， Liao CX， et al. Effect of inhaling specific phosphodiesterase inhibitor on lung injury induced by cardiopulmonary bypass. Zhonghua Yi Xue Za Zhi （Taipei）， 2011， 91 （20）：1401-1404.
13. 　Welters ID， Feurer MK， Preiss V， et al. Continuous S- （＋）-ketamine administration during elective coronary artery bypass graft surgery attenuates pro-inflammatory cytokine response during and after cardiopulmonary bypass. Br J Anaesth， 2011， 106 （2）：172-179.
14. 　Morgan C， Zappitelli M， Gill P. Statin prophylaxis and inflammatory mediators following cardiopulmonary bypass：a systematic review. Crit Care， 2009， 13 （5）：R165.
15. 　Martínez-Comendador JM， Alvarez JR， Mosquera I， et al. Preoperative statin treatment reduces systemic inflammatory response and myocardial damage in cardiac surgery. Eur J Cardiothorac Surg， 2009， 36 （6）：998-1005.
16. 　余杨，何德沛，申林，等. 核转录因子-κB抑制剂对体外循环肺损伤的保护作用. 中国胸心血管外科临床杂志， 2007， 14 （5）：86-88.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Heparin-free Cardiopulmonary Bypass and Early Systemic Inflammatory Response

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